Pharmacokinetic properties and bioequivalence of two sulfadoxine/pyrimethamine fixed-dose combination tablets: a parallel-design study in healthy Chinese male volunteers.

BACKGROUND: Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe(®), coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability of the sulfadoxine/pyrimethamine FDC tablet in the World Health Organization's (WHO) Prequalification of Medicines Programme, as well as to obtain marketing authorization in China. OBJECTIVE: The aim of the present study was to compare the pharmacokinetic profiles between a new generic and the branded reference formulation of sulfadoxine/pyrimethamine FDC tablets, and to assess the bioequivalence of the 2 products in healthy Chinese volunteers. METHODS: This single-dose, open-label, randomized, parallel-group study was conducted in healthy Chinese male volunteers who were randomly assigned (1:1) to receive a single 1500/75-mg dose (3 × 500/25-mg tablets) of either the test or reference formulation after a 12-hour overnight fast. Seventeen blood samples were obtained over a 168-hour interval, and plasma concentrations of sulfadoxine and pyrimethamine were determined by 2 separate validated liquid chromatography-isotopic dilution mass spectrometry methods. Pharmacokinetic properties (C(max), AUC(0-72), AUC(0-168), and T(max)) were calculated and analyzed statistically. The 2 formulations were to be considered bioequivalent if 90% CIs for the log-transformed ratios of C(max) and AUC(0-72) were within the predetermined bioequivalence range of 80% to 125%, in accordance with the guidelines of WHO and China's Food and Drug Administration (FDA). Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead ECGs, and subject interviews on adverse events (AEs). RESULTS: Forty-six healthy subjects completed the study. The mean values of sulfadoxine C(max) (183.07 and 165.15 mg/L), AUC(0-72) (11,036.52 and 10,536.78 mg/L/h), and AUC(0-168) (22,247.05 and 21,761.02 mg/L/h) were not significantly different between the test and reference formulations, respectively. The same was true for pyrimethamine (0.55 and 0.58 mg/L, 29.85 and 31.44 mg/L/h, and 56.18 and 59.27 mg/L/h, respectively). The 90% CIs for the log-transformed ratios of C(max), AUC(0-72), and AUC(0-168) of both sulfadoxine (105.4%-116.6%, 99.3%-110.6%, and 96.4%-108.1%) and pyrimethamine (88.8%-100.9%, 89.5%-101.0%, and 88.3%-101.6%) were within the acceptance limits for bioequivalence. A total of 7 mild AEs were reported in 7 subjects (15.2%). CONCLUSIONS: The findings from this single-dose (1500/75-mg) study suggest that the test and reference formulations of sulfadoxine/pyrimethamine FDC 500/25-mg tablet have similar pharmacokinetic profiles both in terms of rate and extent of absorption. The formulations met WHO's and China's FDA regulatory criteria for bioequivalence in these healthy Chinese volunteers under fasting conditions. Both formulations were generally well-tolerated.

[Surveillance on iodized salt in China, in 2006].

OBJECTIVE: To understand the national situation of quality and consumption of iodized salt at production and household levels. METHODS: Detailed surveillance method could be found in 'national iodized salt surveillance scheme', issued by MOH in 2004. The iodine concentrations in salt (except some special kinds of salt) were detected by direct titration with national standard of GB/T 13025.7-1999, in which the iodine content in qualified iodized salt was set as between 20 and 50 mg/kg and that in non-iodized salt was set as below 5 mg/kg. RESULTS: At production level, the national lot qualified rate was 98.36% and all the provincial lot qualified rate of production level was over 90%. At household level, the national iodized salt coverage rate of household was 96.87% and the national qualified iodized salt coverage rate was 93.75%. 4 provinces (Tibet, Hainan, Xinjiang and Guangdong) had an iodized salt coverage rate lower than 90%. Further, the qualified iodized salt coverage rate of 5 provinces (Tibet, Hainan, Xinjiang, Guangdong and Qinghai) was below 90%. In 2006,80 counties did not conduct the iodized salt surveillance and non-iodized salt coverage rate of 185 counties was higher than 10%. In the respect of the qualified iodized salt coverage rate at household level, there were about 10 percent lagging behind the national goal that 95% of all the counties in China should achieve virtual elimination of iodine deficiency disorder before 2010. CONCLUSION: At national level,the lot qualified rate at production level and the iodized salt coverage rate at household level maintained comparatively well. However, at county level, there were 75 counties whose iodized salt coverage rate was below 70%.

[Study on the national program of monltoring the iodized-salt situation in 2004].

OBJECTIVE: To understand the situation of quality and consumption of iodized-salt at production and household levels through monitoring on salt. METHODS: 9 townships were chosen in each county at different locations. In each township, two villages were selected in the center of the township and another two villages in remote settings. In each village, 8 households were selected for salt collection. The iodine concentrations in salt (except some special kinds of salt) were detected by method of direct titration with criteria in GB/T 13025.7-1999, in which the iodine content in qualified iodized-salt was set as 20 to 50 mg/kg and that in non-iodized-salt it was below 5 mg/kg. RESULTS: Except for Tibet and Xinjiang, lot qualified rate of production level was 97.39% at the national level. Except for Xinjiang, the qualified rate of iodized-salt of household level was 96.45%; qualified iodized-salt coverage rate was 93.47%; noniodized-salt coverage rate was 3.09%. The results of the iodized-salt monitoring in 2004 maintained almost the same level as that in 2002. At production level,lot qualified rate of iodized-salt in Sichuan and Qinghai provinces were below 90%. At household level the qualified rate of iodized-salt in Sichuan and Hainan were below 90%. The coverage rates of qualified iodized-salt were below 90% for the total 7 provinces. In 5 provinces, the non-iodized-salt coverage rates were above 10%. CONCLUSIONS: At national level the qualification of iodized-salt at production level was satisfactory. The coverage rates of qualified iodized-salt were below 90% not only in western but in some eastern provinces(including Beijing), which indicated that importance should be attached to the western areas and some newly discovered areas with problems as well. Through continual improvement of qualified iodized-salt coverage, sustained IDD elimination will be achieved.